• Project Leader, Masayuki Igarashi

Tuberculosis (TB) has been a serious problem in the world. In 2008, the World Health Organization (WHO) reported the alarmig fact that incidence was 9.3 million and 1.3 million people dead becouse of TB.

Accompanied with a large number of patient, inadequate treatment or use of drug causes drug-resistance such as multi-drug resistant tuberculosis (MDR-TB) defined by resistance to isoniazid and rifampin and more virulent, extensively drug-resistant tuberculosis (XDR-TB). The latter TB is resistant to isoniazid and rifampin among first-line anti-tubercular drugs, fluoroquinolone, and one of three second-line drugs, capreomycin, kanamycin, and amikacin. In such a serious situation, development of a new drug with new chemical structure and different mode of action compared with existing drugs is extremely desired.

Our institute was established in 1962 by Dr Hamao Umezawa who discovered kanamycin, one of the second-line drugs above mentioned. Since then, we have continued to develop new drugs, especially been interested in anti-TB drugs.

In 2003, we discovered anti-TB antibiotics, caprazamycins produced by the Actinomycete strain, Streptomyces sp. MK730-62F2.

(fig.1 Structure of caprazamycin B)
Structure of caprazamycin B

After the SAR, we chose CPZEN-45 as a TB-drug candidate. CPZEN-45 is effective against both sensitive and resistant strains of TB.

In 2008, we joined "The Lilly TB Drug Discovery Initiative" and collaborate on further studies for developing this candidate in a short time.